Statins as antiinflammatory and immunomodulatory agents: A future in rheumatologic therapy?

Abeles, Aryeh M.; Pillinger, Michael H.

doi:10.1002/art.21521

Cited by 134 publications

(99 citation statements)

References 174 publications

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“…Our study suggests that statins have minimal or no effect on these eye diseases. We found no evidence to support a reported protective effect against Parkinson's disease [35], multiple sclerosis [36], rheumatoid arthritis [37,38], psoriasis [39] or effects on systemic lupus erythematosus [39,40]. Concern that statins are associated with an increased risk of upper motor neuron lesions was raised based on spontaneous reports to the World Health Organization Programme for International Drug Monitoring [13].…”

Section: Comparison Of Results With Previous Studiesmentioning

confidence: 71%

“…Many disease processes have been suggested to be affected by statin use, including protection from infectious processes [5]; effects on cancer [6,7]; protection against dementia [8] and fractures [9]; effects on the eye [10,11] and a range of neurological [12,13] and immune-mediated diseases [14]. However, outside clinical trials, exposure to statins is not randomized, but is determined by a wide range of health-related factors.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of statins on a wide range of health outcomes: a cohort study validated by comparison with randomized trials

Smeeth

Douglas

Hall

et al. 2008

Brit J Clinical Pharma

205

198

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The effect of statins on cardiovascular outcomes is well established.• Effects on numerous other health outcomes have been claimed, but results have been inconsistent.• Previous observational studies may have been affected by selection bias and confounding. WHAT THIS STUDY ADDS• This study was larger and more statistically powerful than the combined total of data from all randomized trials of statins undertaken to date.• The validity of the study is supported by findings for vascular outcomes being comparable to those observed in large randomized controlled trials.• There was little evidence to support effects of statins beyond their established effects on cardiovascular disease. AIMSTo assess the effect of statins on a range of health outcomes. METHODSWe undertook a population-based cohort study to assess the effect of statins on a range of health outcomes using a propensity score-based method to control for differences between people prescribed and not prescribed statins. We validated our design by comparing our results for vascular outcomes with the effects established in large randomized trials. The study was based on the United Kingdom Health Improvement Network database that includes the computerized medical records of over four and a half million patients. RESULTSPeople who initiated treatment with a statin (n = 129 288) were compared with a matched sample of 600 241 people who did not initiate treatment, with a median follow-up period of 4.4 years. Statin use was not associated with an effect on a wide range of outcomes, including infections, fractures, venous thromboembolism, gastrointestinal haemorrhage, or on specific eye, neurological or autoimmune diseases. A protective effect against dementia was observed (hazard ratio 0.80, 99% confidence interval 0.68, 0.95). There was no effect on the risk of cancer even after Ն8 years of follow-up. The effect sizes for statins on vascular end-points and mortality were comparable to those observed in large randomized trials, suggesting bias and confounding had been well controlled for. CONCLUSIONSWe found little evidence to support wide-ranging effects of statins on health outcomes beyond their established beneficial effect on vascular disease.

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Section: Comparison Of Results With Previous Studiesmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Effect of statins on a wide range of health outcomes: a cohort study validated by comparison with randomized trials

Smeeth

Douglas

Hall

et al. 2008

Brit J Clinical Pharma

205

198

View full text Add to dashboard Cite

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“…Statins are best known for their capacity to inhibit cholesterol synthesis, but they also have anti-inflammatory effects by, for example, inhibiting leukocyte-endothelial adhesion, thereby muting the production of pro-inflammatory cytokines and modulating regulatory T cell activity 203,204 . Anecdotal stories suggest that local physicians in Sierra Leone successfully used two statins, atorvastatin and irbesartan 205 .…”

Section: Cytokine Stormmentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

106

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| The filoviruses -Ebola virus and Marburg virus -cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus. This Review briefly discusses these failures and what has been learned from these experiences, and summarizes the current status of post-exposure medical countermeasures in development, including antibodies, small interfering RNA and small molecules. We outline how our current knowledge could be applied to the identification of novel interventions and ways to use interventions more effectively. R E V I E W SNATURE REVIEWS | DRUG DISCOVERY VOLUME 17 | JUNE 2018 | 413 © 2 0 1 8 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . AstheniaMuscular weakness. MyalgiaMuscular pain. ArthralgiaJoint pain. LeukopeniaA condition of having a low number of circulating leukocytes, including neutrophils, eosinophils, basophils, lymphocytes and monocytes. LymphocytopeniaA condition of having a low number of circulating leukocytes, including natural killer cells, T cells and B cells. ThrombocytopeniaA condition of having a low number of circulating thrombocytes, also known as platelets.and Ebolavirus. The Marburgvirus genus contains a single species, Marburg marburgvirus, which contains two members, Marburg virus (MARV) and Ravn virus (RAVV). The Ebolavirus genus consists of five distinct species: Bundibugyo ebolavirus (BDBV), Reston ebolavirus (RESTV), Sudan ebolavirus (SUDV), Tai Forest ebolavirus (TAFV; previously termed 'Côte d'Ivoire ebolavirus' but more commonly known as 'Ivory Coast ebolavirus') and Zaire ebolavirus (EBOV). MARV, RAVV, BDBV, SUDV and EBOV are important human pathogens, with case fatality rates often up to 90% for MARV, RAVV and EBOV, and around 55% for SUDV 8,10 . On the basis of two small outbreaks in 2007 and 2012, BDBV seems to be the least pathogenic, with a case fatality rate of about 40-48% 11,12 . In 1994, TAFV was associated with a number of deaths in chimpanzees and a single symptomatic but non-lethal human infection in the Republic of Côte d'Ivoire 13,14 . RESTV is lethal for macaques but is not thought to cause disease in humans 15 . An outbreak of RESTV was reported in pigs in the Philippines in 2008; however, it remains uncertain whether the disease observed in the pigs was caused by RESTV or other agents reported to have co-infected the animals 16 . Clinical manifestationsClinical and laboratory signs of disease caused by filovirus infection are nonspecific and usually associated with an incubation period of 2-21 days (mean 4-10 days) 8,17 . Illness begins with an abrupt onset of fever, astheni...

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“…Previous investigations have shown that statins have a wide range of effects on cells and tissues involved in inflammation (37); however, animal studies on the therapeutic effects of systemically delivered statins in inflammatory arthritis have yielded conflicting results (21)(22)(23). Although the statin doses used in the mouse models (up to 40 mg/kg per day [21,22], equivalent to a daily human dose of 3.25 mg/kg [40]) were higher than those used in standard therapy in humans (0.1-1.0 mg/kg per day) (41), the amount of drug reaching the joints may be low since statins are designed to act primarily in the liver (42).…”

Section: Discussionmentioning

confidence: 99%

Simvastatin inhibits cytokine‐stimulated Cyr61 expression in osteoblastic cells: A therapeutic benefit for arthritis

Kok

Hou

Hong

et al. 2011

Arthritis & Rheumatism

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Objective. To examine the effects of proinflammatory cytokines on Cyr61 expression in osteoblastic cells and the modulatory action of simvastatin, to assess the role of CREB in Cyr61 induction, and to investigate the relationship of osteoblastic expression of Cyr61 to disease progression in experimental arthritis.Methods. Cyr61 expression and CREB phosphorylation at serine 133 were examined by Western blotting. Promoter activity of Cyr61 was assessed by luciferase assay with promoter deletion/mutagenesis and forced expression/gene silencing of CREB. Interaction between CREB and the Cyr61 promoter was evaluated by electrophoretic mobility shift assay and chromatin immunoprecipitation. CCL2 expression was examined by Northern blotting and enzyme-linked immunosorbent assay. In rats with collagen-induced arthritis (CIA), osteoblastic expression of Cyr61 was examined by immunohistochemistry, and disease progression was assessed by clinical, radiographic, and histologic examination. Results. In primary human osteoblasts and U2OS

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Statins as antiinflammatory and immunomodulatory agents: A future in rheumatologic therapy?

Cited by 134 publications

References 174 publications

Effect of statins on a wide range of health outcomes: a cohort study validated by comparison with randomized trials

Effect of statins on a wide range of health outcomes: a cohort study validated by comparison with randomized trials

Post-exposure treatments for Ebola and Marburg virus infections

Simvastatin inhibits cytokine‐stimulated Cyr61 expression in osteoblastic cells: A therapeutic benefit for arthritis

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